INTERACTION OF THE HUMAN ANDROGEN RECEPTOR TRANSACTIVATION FUNCTION WITH THE GENERAL TRANSCRIPTION FACTOR TFIIF

The human androgen receptor (AR) is a ligand-activated transcription f actor that regulates genes important for male sexual differentiation a nd development. To better understand the role of the receptor as a tra nscription factor we have studied the mechanism of action of the N-ter minal transactivation function. In a protein-protein interaction assay the AR N terminus (amino acids 142-485) selectively bound to the basa l transcription factors TFIIF and the TATA-box-binding protein (TBP), Reconstitution of the transactivation activity in vitro revealed that AR(142-485) fused to the LexA protein DNA-binding domain was competent to activate a reporter gene in the presence of a competing DNA templa te lacking LexA binding sites. Furthermore, consistent with direct int eraction with basal transcription factors, addition of recombinant TFI IF relieved squelching of basal transcription by AR(142-485). Taken to gether these results suggest that one mechanism of transcriptional act ivation by the AR involves binding to TFIIF and recruitment of the tra nscriptional machinery.